M60 - Polygenic Risk Scores And Substance Abuse Comorbidity In Patients With Schizophrenia And Bipolar Disorders

Abstract

Background Introduction Cannabis is the most widely used illicit drug in the world. It is well established that substance abuse comorbidity i.a. cannabis is much higher among patients with schizophrenia (SCZ) and bipolar disorders (BD) than in the general population. However, the relationship between SCZ, BD and cannabis might be more complicated than it initially seems. Previous studies have revealed that a genetic predisposition to SCZ might be associated with increased of cannabis in healthy individuals. Given this relationship, we intended to study whether polygenic risk scores (PRS) for SCZ predict cannabis in patients with SCZ and BD. In addition we want to test whether cannabis PRS have an impact on cannabis in these two subgroups. Methods 1. In a sample of 630 individuals (N= 367 SCZ, and N= 263 BD) in the KFO/PsyCourse cohort (www.kfo241.de; www.PsyCourse.de), we tested whether PRS for SCZ predict cannabis in patients with SCZ and BD. PRS reflect the cumulative burden of risk alleles carried by an individual according to the well-powered genome-wide association study (GWAS) investigated by the Psychiatric Genomics Consortium (PGC). 2. We will test whether cannabis PRS calculated according to a recent GWAS from the International Cannabis Consortium (ICC) explains cannabis in patients with SCZ and BD in our cohort. 3. We tested the replicability of our results in an independent sample from the USA (GAIN/TGen), with a sample size of 1.150. Results First results: PRS for SCZ showed positive associations (R2=3.5 % p=0.0067) for “use” versus “never use” of cannabis in BD with the strongest association of PRS that were based on SNPs with a p-value ≤0.0001 in the original SCZ GWAS. This finding replicated in an independent sample of BD patients where higher PRS were also associated with a higher probability of cannabis (OR=1.20 for increase of PRS by 1 sample sd, p=0.0105). Comparisons of PRSs in the groups vs. „never use showed repeated nominal significance (p Discussion Conclusion: First results suggest that individuals with BD and an increased polygenic risk for SCZ are more likely to cannabis. The association between BD and cannabis might be not simply one of an environmental risk factor, but rather involves gene–environment interaction, as individuals choose and shape their own environment according on their own innate preferences.